Retrospective Analysis of the Safety and Efficacy of Interleukin-2 After Prior VEGF-targeted Therapy in Patients With Advanced Renal Cell Carcinoma
Retrospective Analysis of the Safety and Efficacy of Interleukin-2 After Prior VEGF-targeted Therapy in Patients With Advanced Renal Cell Carcinoma
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DOI：
10.1097/cji.0b013e3181952b1d
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发表时间：
2009-02-01
影响因子：
3.9
通讯作者：
McDermott, David F.
中科院分区：
文献类型：
--
作者：
Cho, Daniel C.;Puzanov, Igor;McDermott, David F.
靶向血管内皮生长因子（VEGF）信号的药物已被提倡作为晚期肾癌的一线治疗。白细胞介素2 （IL-2）治疗对vegf靶向治疗耐药后的作用仍未探索。我们对先前接受过vegf靶向治疗的患者进行了IL-2治疗的耐受性和疗效的回顾性分析。对23例连续接受补救性IL-2治疗的患者进行分析。15例患者先前接受过酪氨酸激酶抑制剂（TKIs）（索拉非尼或舒尼替尼），而8例患者单独接受过贝伐单抗。23例患者中有6例未接受第1周期治疗的第2周。所有6例患者均曾接受tki治疗。在既往接受TKI的患者中，严重心脏毒性（包括1例心源性猝死）的发生率为40%(95%可信区间，16.3-67.7%)，显著高于历史经验的预期。只有1或23例患者继续接受第二周期的IL-2治疗。没有患者对治疗产生部分或完全反应。这项回顾性分析强调了在vegf靶向TKI治疗后接受IL-2治疗的患者的意外和严重的心脏毒性。认为在TKI治疗后可以安全地给予IL-2治疗的假设可能不成立。进一步检查这种顺序方法的安全性是必要的，更谨慎的患者选择似乎是必要的。
Agents targeting vascular endothelial growth factor (VEGF) signaling have been advocated as frontline therapy for advanced renal cancer. The role of interleukin 2 (IL-2) therapy after resistance to VEGF-targeted therapy remains Unexplored. We conducted a retrospective analysis of the tolerability and efficacy of IL-2 therapy in patients who had previously received VEGF-targeted therapy. Twenty-three consecutive patients who received salvage IL-2 therapy were analyzed. Fifteen patients had received prior tyrosine kinase inhibitors (TKIs) (sorafenib or sunitinib), whereas 8 patients had received bevacizumab alone. Six of 23 patients did not receive week 2 of cycle 1 of treatment. All 6 of these patients had received prior TKIs. The incidence of severe cardiac toxicities, including 1 sudden cardiac death, in patients receiving prior TKI was 40% (95% confidence interval, 16.3-67.7%), significantly higher than what is expected from historical experience. Only 1 or 23 patients proceeded to receive a second cycle of IL-2. No patients achieved a partial or complete response to therapy. This retrospective analysis highlights inexpected and severe cardiac toxicities in patients receiving IL-2 after VEGF-targeted TKI therapy. The assumption that IL-2 therapy can be safely administered after TKI therapy may not be valid. Further examination of the safety of this sequential approach is necessary and more cautious patient selection seems warranted.